Female Reproductive System ORGAN SYSTEMS

Polycystic ovary syndrome (PCOS/PCOD)

Polycystic Ovarian Syndrome (PCOS), also referred to as hyperandrogenic anovulation (HA), or Stein–Leventhal syndrome is a symptom complex of multifactorial and polygenic pathology characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphologic features.

Polycystic Ovarian Syndrome (PCOS), also referred to as hyperandrogenic anovulation (HA), or Stein–Leventhal syndrome is a symptom complex of multifactorial and polygenic pathology characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphologic features.

  • M/C endocrine disorder of women of reproductive age
  • M/C pathological cause for hirsutism in women
    • M/C cause of rapid-onset hirsutism: Testosterone producing tumour
  • M/C cause of anovulatory infertility


Multi- factorial and polygenic aetiology:

Aetiology of PCOS appears to be ‘multi- factorial and polygenic’. Both nature and nurture seem to play a role in contributing to PCOS. It has been found to cluster in families, particular in those with history of polycystic ovaries (PCO), non-insulin dependent diabetes mellitus, cardiovascular disease (CVD) and breast cancer. Meanwhile, excessive intake of excitatory amino acids that can affect the pituitary regulation of the ovary cycles such as monosodium glutamate (MSG), exposure to endocrine-disrupting chemicals such as pesticides, and sedentary lifestyle are also believed to result in PCOS.
  • Idiopathic (M/C)
  • Obesity
  • Lack of exercise
  • Family history of PCOS
    • M/C gene mutation: Cyp 21 gene
  • Insulin resistance
Environmental factors influencing PCOS. Intrauterine growth retardation and insulin resistance as examples of non-genetic inheritance are markedly influenced by environmental factors. Insults during pregnancy might result in intrauterine growth retardation, inducing a thrifty phenotype in small for gestational age babies (red). The insulin resistance characteristic of this phenotype is an example of permanent programming of metabolic function and could lead to overweight issues in childhood. These children might develop hypertension, glucose intolerance and polycystic ovary syndrome (PCOS) later in life (especially if these individuals are exposed to environmental risk factors such as a sedentary lifestyle, a diet rich in saturated fat, smoking and excessive alcohol consumption), which might also cluster in certain families because exercising and diet are heavily influenced by parental habits. However, if the unhealthy environment changes to healthier options (adequate diet, active lifestyle and no toxic habits), then the non-genetic inheritance might be prevented, at least in theory (blue). | Escobar-Morreale, H. F., Luque-Ramirez, M. & San Millan, J. L. The molecular-genetic basis of functional hyperandrogenism and the polycystic ovary syndrome. Endocr. Rev. 26, 251–282 (2005).

Syndromic associations:

These usually result in exaggerated phenotypes of PCOS
  • HAIR-AN syndrome (hyperandrogenism, insulin resistance and acanthosis nigricans)
  • Metabolic X syndrome


Androgen excess: Central event in the pathogenesis of PCOS

PCOS is characterized by hypothalamic–pituitary–ovary axis dysfunction and anovulation but, unlike other causes of ovulatory failure that feature insufficient ovarian follicle growth or suppressed gonadotropin secretion (or both), PCOS typically includes androgen excess and subtle alterations (not detected by routine tests) in serum levels of gonadotropins and estrogens. PCOS is characterized by increased levels of circulating androgen, polycystic ovarian morphology (PCOM), arrested follicle development, and anovulatory infertility.
Rotstein, A. (2017). Polycystic ovarian syndrome (PCOS) | McMaster Pathophysiology Review. [online] Available at: [Accessed 19 Sep. 2017].

The syndrome is also associated with persistently rapid gonadotropin-releasing hormone pulses, an excess of luteinizing hormone, and insufficient follicle-stimulating hormone (FSH) secretion, which contribute to excessive ovarian androgen production and ovulatory dysfunction.

  • ↑ Gonadotropins → ↑ GnRH pulse frequency → ↑ LH/FSH ratio (2:1) → ↑ Androgens
The pathophysiology of PCOS. | Azziz, R., Carmina, E., Chen, Z. et al. Polycystic ovary syndrome. Nat Rev Dis Primers 2, 16057 (2016).

Follicular arrest:

Role of AMH in folliculogenesis. AMH has an inibitory effect on initial recruitment of primary follicles, on FSH-dependent follicular maturation and selection of dominant follicle, and on FSH-induced aromatase expression on granulosa cells, reducing the conversion of testosterone into estradiol. Higher AMH levels in PCOS patients turns the follicles more resistant to FSH action, culminating in inhibition of follicular maturarion and ovulation, and in inhibiton of aromatase expression, and consequently, leading to hyperandrogenism. | Azziz R, Carmina E, Chen Z, Dunaif A, Laven JS, Legro RS, et al. Polycystic ovary syndrome. Nat Rev Dis Primers. 2016;2:16057.

Insulin resistance:

Insulin resistance, and compensatory hyperinsulinemia enhances ovarian (and adrenal) androgen production and increases androgen bioavailability through reduced levels of sex hormone–binding globulin.
  • Insulin resistance & hyperinsulinemia → ↓ SHBG → ↑ LH → ↑ Androgens
  • Obesity → ↓ SHBG → ↑ LH → Androgens
Pathophysiological heterogeneity in patients with PCOS: Polycystic ovary syndrome (PCOS) is the result of the interaction of a primary abnormality in androgen synthesis (manifesting as androgen excess) with other factors, such as abdominal adiposity (red and white targets), obesity and insulin resistance. At one extreme (*), the disorder in some patients is severe enough to result in PCOS even in the absence of triggering factors (light-blue-shaded woman on the left). At the other extreme (**), a very mild defect in androgen secretion is amplified by the coexistence of abdominal adiposity, obesity and/or insulin resistance (pink-shaded woman on the right). Between the two extremes, there is a spectrum in the severity (range of blue-shaded to pink-shaded women in the middle) of the primary defect in androgen secretion, providing an explanation for the heterogeneity of patients with PCOS with regards to the presence of obesity and metabolic comorbidities. However, all patients share a primary defect in androgen secretion. | Escobar-Morreale, H. F. & San Millan, J. L. Abdominal adiposity and the polycystic ovary syndrome. Trends Endocrinol. Metab. 18, 266–272 (2007). | Escobar-Morreale, H. F., Santacruz, E., Luque-Ramirez, M. & Botella Carretero, J. I. Prevalence of ‘obesity-associated gonadal dysfunction’ in severely obese men and women and its resolution after bariatric surgery: a systematic review and meta-analysis. Hum. Reprod. Update 23, 390–408 (2017).


The symptomatic presentation of PCOS usually varies with age, young women mainly complaining of reproductive and psychological problems while older women complaining of metabolic symptoms


More than 80% of women presenting with symptoms of androgen excess have PCOS
  • Hirsutism (M/C, 70% cases): Excess terminal hair in a male pattern of distribution
    • Sites: Lower abdomen, nipples, chin & upper lip
  • Acne
  • Alopecia
  • Dyslipidemia

Menstrual disturbances:

30% of women with PCOS will have normal menses. Approximately 85%–90% of women with oligomenorrhea have PCOS while 30%–40% of women with amenorrhea will have PCOS
  • Infertility (40% cases)
  • Anovulation/hypoovulation (disturbed LH/FSH levels)
    • 90%–95% of anovulatory women presenting to infertility clinics have PCOS
  • Dysmenorrhoea (increased estrone)
  • Oligo/amenorrhea cycles: ≤ 8/year (90% cases)

Associated metabolic morbidities:

PCOS is associated with high rates of glucose intolerance resulting from defects in insulin action and β-cell function. Obesity substantially exacerbates these defects so obese reproductive-age women with PCOS are at very high rates of glucose intolerance.
  • Insulin resistance:
    • Acanthosis nigrans
    • DM-2 (10% cases)
  • Obesity (low adiponectin levels)
Lanzo E, Monge M, Trent M. Diagnosis and Management of Polycystic Ovary Syndrome in Adolescent Girls. Pediatr Ann. 2015; 44: e223-e230. doi: 10.3928/00904481-20150910-10

Case study


Short term complications:

  • Infertility
  • Hirsutism
  • Irregular menstrual cycles

Long-term complications:

  • Endometrial carcinoma (↑ estrone)
  • Breast cancer
  • Diabetic mellitus
  • Cardiovascular disesase

Obesity complications:

  • Sleep apnoea
  • Diabetic mellitus
  • Metabolic syndrome
  • Depression


PCOS is a diagnosis of exclusion, based primarily on the presence of hyperandrogenism, ovulatory dysfunction and PCOM.

Algorithm for the aetiological diagnosis of women thought to have PCOS. An unusual clinical presentation should immediately be suspected to be an androgen-secreting neoplasm that must be ruled out by appropriate adrenal and ovarian imaging techniques and might even require venous sampling (left arm of flowchart). A typical peripubertal, slow and progressive presentation requires careful assessment of clinical hyperandrogenism, hyperandrogenaemia, ovulatory function and ovarian morphology and exclusion of secondary aetiologies such as non-classic congenital adrenal hyperplasia (NCCAH) or hyperprolactinaemia. | Escobar-Morreale, H. F. et al. Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society. Hum. Reprod. Update 18, 146–170 (2012).

Diagnostic criteria:

Diagnostic criteria for PCOS have been offered by 3 groups. Each issuing group considers PCOS a diagnosis of exclusion, and other diagnoses, such as congenital adrenal hyperplasia, nonclassic adrenal hyperplasia, Cushing syndrome, androgen-secreting tumor, idiopathic hyperandrogenism, idiopathic hirsutism, hyperprolactinemia, and thyroid disorders must be excluded.
  1. National Institutes of Health/National Institute of Child Health and Human Disease (NIH/NICHD) | 1992
  2. European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE/ASRM) “Rotterdam criteria” | 2004
  3. Androgen Excess and PCOS Society | 2006
Diagnostic criteria and phenotypes of PCOS. | Azziz, R., Carmina, E., Chen, Z. et al. Polycystic ovary syndrome. Nat Rev Dis Primers 2, 16057 (2016).

Rotterdam criteria:

At Least 2 criterias required
Signs and symptoms in patients with PCOS | El Hayek, S., Bitar, L., Hamdar, L. H., Mirza, F. G., & Daoud, G. (2016). Poly Cystic Ovarian Syndrome: An Updated Overview. Frontiers in physiology, 7, 124.

Rotterdam criteria divided the disease into four phenotypes:

  1. Frank/classic polycystic ovary PCOS (chronic anovulation, hyperandrogenism, and polycystic ovaries)
  2. Classic non-polycystic ovary PCOS (chronic anovulation, hyperandrogenism, and normal ovaries)
  3. Non-classic ovulatory PCOS (regular menstrual cycles, hyperandrogenism, and polycystic ovaries)
  4. Non-classic mild or normoandrogenic PCOS (chronic anovulation, normal androgens, and polycystic ovaries)
The heterogeneous nature of PCOS. Polycystic ovary syndrome (PCOS) is a heterogeneous disorder in terms of phenotypes and clinical manifestations and in terms of metabolic consequences. The most severe classic phenotypes (highlighted in dashed outline), consisting of hyperandrogenism (symptoms include hirsutism, acne, alopecia and seborrhoea) and oligo-ovulation (symptoms include menstrual dysfunction, subfertility and endometrial hyperplasia), are associated with the most severe insulin resistance and metabolic |

Modified Ferriman-Gallway index:

9 sites examined for hirsutism. Score of ≥ 8 diagnostic (maximum score 36)
Modified Ferriman-Gallwey Scoring System. This semi-objective scoring system is based on observation of nine body areas including upper lip, chin, chest, arm, upper abdomen, lower abdomen, upper back, lower back, and thighs. The areas are scored from 1 (minimal terminal hairs present) to 4 (equivalent to a hairy man). If no terminal hairs are noted in the specific body area being examined the score is zero. Clinically terminal hair hairs can be distinguished from vellus hairs primarily by their length (i.e. greater than 0.5 cm) and the fact that they are usually pigmented | Ricardo Azziz, copyright 1997

2-h glucose challenge test:

Considering the baseline defects in insulin sensitivity and secretion in PCOS and the deleterious impact of obesity on these measures, women with this condition are expected to have a high prevalence of impaired glucose tolerance (IGT), defined by a 2h post-challenge glucose level 140–200 mg/dl and type 2 diabetes.
Women with PCOS (black bars) had much higher prevalence of abnormal glucose tolerance compared to control women of similar ethnicity, age, and weight (gray bars) (P=0.02) as well as compared to reproductive-age women from the Second National Health and Nutrition Examination Survey (NHANES) (white bars). | Sam S. (2007). Obesity and Polycystic Ovary Syndrome. Obesity management, 3(2), 69–73.

Transvaginal sonography (TVS):

  • Multiple (≥ 12) cysts measuring 2-9mm
  • “Chain of pearl” or “ring of pearls” appearance in ovaries
  • Increased ovarian stroma
  • Ovarian volume > 10ml
Ultrasound of a polycystic ovary: Left ovary slightly enlarged, presenting sub-centimeter transonic images, indicating a certain degree of bilateral ovarian dystrophy. | Anne Mousse – CC0,

Differential diagnosis:

  • Other causes of oligomenorrhea/anovulation:
    • Prolactin-secreting tumour
    • Hyperthyroidism
    • Hypothyroidism
    • Hypogonadotropic hypogonadism
    • Premature ovarian failure (POF)
  • Other androgen excess disorders:
    • Non-classical congenital adrenal hyperplasia (NC-CAH)
    • Cushing’s syndrome
    • Androgen-secreting tumors
    • Hyperprolactinemia
    • Thyroid diseases
    • Drug-induced androgen excess


Treatment should be tailored to the complaints and needs of the patient and involves targeting metabolic abnormalities through lifestyle changes, medication and potentially surgery for the prevention and management of excess weight, androgen suppression and/or blockade, endometrial protection, reproductive therapy and the detection and treatment of psychological features.

Algorithm for the management of clinical hyperandrogenism. Lifestyle recommendations might benefit all patients, and cosmetic procedures can be freely used for all patients. By contrast, drug treatment must be restricted to women not seeking to conceive, and this restriction applies even to topical drugs, such as eflornithine, which might be teratogenic. For women not seeking to conceive, clinical hyperandrogenism is best treated through the use of an oral contraceptive pill containing an anti-androgenic or neutral progestin. When the response to oral contraceptive pills is unsatisfactory or these drugs are contraindicated, anti-androgens might be added to oral contraceptive pills or used as single agents (provided that secure contraception is warranted), respectively. | Escobar-Morreale, H. F. et al. Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society. Hum. Reprod. Update 18, 146–170 (2012).

Medical management:

  • Menstrual disturbances: OCPs
  • Obesity: Lifestyle modifications
  • Insulin resistance: Metformin
  • Hirsutism/acne: OCP + cyproterone acetate
  • Infertility: Clomiphene citrate
20150321170559_30116 (2017). Infertility Treatment in Kolkata, Polycystic Ovary Syndrome. [online] Available at: [Accessed 19 Sep. 2017].

Surgical management:

Indicated in failed medical therapy, ovarian hyperstimulation, infertility or previous pregnancy losses. Surgery restores endocrine milieu and improves fertility for a year or so. After a year, pelvic adhesions may reduce the fertility.
  • Laparoscopic drilling of ≤ 4 cysts in each ovary by laser/unipolar electrocautery


Lyons, J. I., Kerr, G. R. and Mueller, P. W. (2017) ‘Fragile X Syndrome’, The Journal of Molecular Diagnostics. Elsevier, 17(5), pp. 463–471. doi: 10.1016/j.jmoldx.2015.04.006.

2 replies on “Polycystic ovary syndrome (PCOS/PCOD)”

Your caricatures of the ovary is highly offensive, it does not depict all what is PCOS there are some who are deeply affected who are skinny, who experience this at a young age due to genetics. Not to mention a A lot of woman in the pcos community feel ugly to just see it in that context just adds to the problem.

Read the article. Most of the things described are in percentages (as with all the other articles) because that’s how we’re built and are still just understanding the human body.

The cover image is just a brief representation of the syndrome. I haven’t dealt with the entirety of the disease as it’s beyond the scope of the website. This article is just a brief introduction for anyone interested in learning about the disease.

Taking offence on a medical article is simply absurd as nothing on this website has anything to do with people’s opinions or feelings. This is just a portal for brief self-contained explanations of the various human diseases. You can always choose not to visit the website if you’re offended by the contents of the website.

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